‘The MMR-autism theory? There’s nothing in it’

‘If the MMR vaccine was not the cause of my son’s autism, then why has he got traces of measles virus in his bowels?’

This was the question put to me five years ago by one of the parents involved in the litigation against the measles, mumps and rubella vaccine (MMR), who was a passionate supporter of the campaign led by the former Royal Free Hospital researcher Andrew Wakefield who first claimed a link between MMR and autism. The claim, made in 2002 by a team led by Dublin pathologist John O’Leary, that the measles virus RNA had been detected in gut biopsies of children with autism and gastro-intestinal disturbances, appeared to provide powerful vindication for Wakefield’s hypothesis that a distinctive inflammatory bowel condition – dubbed ‘autistic enterocolitis’ – was the mediating link between MMR and autism.

Testimony in a US court last week by London-based molecular biologist Stephen Bustin comprehensively exposed the unreliability of O’Leary’s findings, based on an investigation of his laboratory carried out in early 2004. ‘It has been incredibly frustrating’, Professor Bustin told me on his return from the USA. ‘For three years we have been unable [for legal reasons] to reveal our findings. Now, based on the publicly available information, I want to get the message out about the O’Leary/Wakefield research: there’s nothing in it.’

Bustin’s revelations follow a series of studies, using the most rigorous analysis techniques, which have failed to replicate O’Leary’s results, while other researchers have disputed the existence of ‘autistic enterocolitis’ as a distinctive disease entity (see footnotes 1-3). All these results are reassuring to parents of autistic children, whose anxieties have been needlessly provoked by the Wakefield campaign. Parents facing decisions about immunisation can also be reassured that the MMR-autism scare has been shown to have no basis in science.

Though it is good news for parents, the testimony of Bustin and other expert witnesses was yet another blow for the anti-vaccine campaigners as Andrew Wakefield returns to London next week from his new base in a private clinic in Texas to face charges of professional misconduct at the General Medical Council.

The hearings in the USA mark the culmination of two parallel anti-vaccine campaigns. In the UK, following Wakefield’s now notorious 1998 paper in the Lancet, which first advanced the MMR-autism thesis, parents of more than 1,400 children were drawn into litigation against vaccine manufacturers. This collapsed in 2004 when the Legal Services Commission realised that, in the absence of scientific evidence for the thesis, the claim had no chance of succeeding. Meanwhile in the USA, campaigners blame the mercury-based preservative thimerosal in some vaccines for the apparent increase in the prevalence of autism. The facts that the prevalence of autism has continued to rise after the removal of thimerosal from vaccines and that MMR has never contained thimerosal have not deterred campaigners from trying to link mercury and MMR in the causation of autism, through a series of speculative and improbable pathways.

In the ‘omnibus autism proceedings’ in the US Court of Federal Claims in Washington DC, the families of more than 4, 800 children are claiming damages from the $2.5billion government fund set aside to compensate people harmed by vaccination. Over 12 days last month the court heard the first test case put forward by the petitioners – that of 12-year-old Michelle Cedillo, whose parents believe that the combination of early childhood immunisations containing thimerosal with MMR at 16 months resulted in the development of autism, inflammatory bowel disease and a range of additional disabilities.

Unfortunately for the petitioners, and to the embarrassment of some of their supporters, there was no real contest – in terms of personal expertise or scientific substance – between the expert witnesses put forward in support of the vaccine-autism theory and those challenging this hypothesis. For example, Marcel Kinsbourne, a long-retired paediatric neurologist who admitted that he had not treated children for 17 years and who has become a professional expert witness, appearing in hundreds of vaccine litigation cases, appeared on questioning to lack any relevant specialist knowledge. Vera Byers, an immunologist, also long-retired, claimed a series of qualifications and academic attachments – including one to Nottingham University – that turned out to be bogus. On questioning, her faculty status at the University of California at San Francisco boiled down to attending courses, using the library, and, bizarrely, ‘going to their parties’.

Another elderly witness, environmental toxicologist Vasken Aposhian from Tucson, Arizona, caused bemusement by apparently denying the significance of dose levels of mercury and conflating in vitro, laboratory studies, with in vivo studies in animals and humans. By contrast, the experts testifying against the vaccine-autism theories included a range of doctors and scientists actively engaged in relevant clinical activity and research, such as the autism specialist Eric Fombonne, now in Montreal, but well-known in the UK for his many years at the Maudsley in London, Cleveland paediatric neurologist Max Wiznitzer, and Baltimore virologist Diane Griffen.

Whereas the petitioners’ experts were unable to produce convincing evidence that mercury and MMR had combined to make Michelle autistic, the respondents’ experts produced powerful evidence against this thesis.

Michelle’s developmental record, including videos at 9, 12 and 15 months – before her MMR – revealed early abnormalities of social interaction, motor delays and other features consistent with a diagnosis of autism;

Blood tests and other investigations revealed no evidence of ‘immune suppression’ or of an abnormal reaction to MMR;

Biopsy specimens taken at endoscopy did not show changes consistent with inflammatory bowel disease.

The respondents’ expert witnesses all expressed their sympathy for Michelle and their respect for her parents; they were equally unanimous in dismissing the notion that any vaccine was the cause of her condition.

Then, in more than 100 pages of testimony, Stephen Bustin, introduced as the author of the ‘bible of PCR’ (‘polymerase chain reaction’ – the basic investigative technique of molecular biology), produced what he describes as ‘just a summary’ of his investigation of the O’Leary lab. One of the first things that he thought ‘peculiar’ when he arrived was that the door of the adjoining lab was labelled ‘Plasmid Room’. As he explained to the court, plasmids are used to replicate DNA molecules in bacteria for experimental purposes; Bustin said he was alarmed because contamination is the bane of PCR studies. ‘You never want to have any plasmid DNA anywhere near your lab when doing PCR’, he says. And yet, he said in the Washington court, there was plasmid DNA, in thousands of millions of copies, just next door to O’Leary’s lab.

Parents who received the results of their children’s biopsy specimens from the O’Leary lab tended to think of the tests in terms of familiar bench tests: you stick litmus paper in acid and it turns red, in alkali and it turns blue. Straightforward, black and white (at least red and blue) easily done, easily confirmed. Nothing could be further from the reality of PCR testing, as Bustin’s exhaustive explanation of the complexities of this technology to the Washington court confirms. His investigation revealed problems in O’Leary’s lab at every step of the process, from the quality of the preparations used to the conduct of the testing, the use of controls, the analysis and interpretation of data. His conclusions were categorical: ‘The assay used was not specific for measles and it was not properly carried out.’ The positive results were positive for DNA – confirming contamination, because ‘if it’s DNA it can’t be measles’ (measles is an RNA virus).

For Bustin it was ‘a scientific certainty’ that the O’Leary lab had failed reliably to identify measles virus RNA in Michelle or any other child (and this includes claims, reported in other studies, that the O’Leary lab had identified measles RNA in blood and cerebrospinal fluid).

Bustin’s devastating testimony effectively destroyed the only piece of positive evidence that has been produced in support of the MMR-autism thesis since it was launched nearly a decade ago. It raises further questions for Professor O’Leary, for the lawyers who led the UK litigation, and for Dr Wakefield.

In May Professor O’Leary delivered his inaugural lecture (on the unrelated subject of cancer genetics) as head of the department of pathology at Trinity College Dublin (4). It seems that his status in Ireland has been unaffected by the damaging disclosures in Washington, which have received little publicity on this side of the Atlantic. Though it is not clear how O’Leary, a pathologist rather than a virologist, became involved in his collaboration with Wakefield, it is known that he set up a commercial company – Unigenetics – which received around £800,000 in legal aid funding from the UK litigation. Though he supervised the lab, it has emerged that much of the work was carried out by graduate – or even undergraduate – students. Though O’Leary has disassociated himself from Wakefield’s campaign against MMR, he has never admitted that the notion – firmly believed by many parents – that his lab had at least confirmed the presence of measles virus in their guts, was entirely false.

Bustin’s report on the O’Leary lab was key to the collapse of the anti-MMR litigation in the UK. When the lawyers at the Legal Services Commission discovered this authoritative investigation concluding that O’Leary’s findings were unreliable they realised that, putting this together with the wider evidence against the MMR-autism thesis, the litigation had no chance of succeeding. Yet the lawyers leading the campaign refused to acknowledge openly that the scientific case against the MMR-autism link was overwhelming and advise their clients to conclude the action. Instead, they continued to pursue the case, allowing it to drag on for a small number of families, acting without legal aid funding, for a further three years.

This not only prolonged the ordeal for these families, it prevented the Bustin study from being made public. Indeed, lawyers for the UK families continued to resist the disclosure of this important investigation until the bitter end – until the eve of the US hearings when the High Court ruled in favour of allowing this testimony, prepared for the UK litigation, to be heard in Washington. (Of the £15million in legal aid funding spent on the MMR litigation, around £8million went to the solicitors, £1.7million to barristers, £4.3million was shared among expert witnesses; the children, of course, were left with nothing.)

When Andrew Wakefield made a rare public appearance in the UK at a (largely sympathetic) conference of parents of autistic children in Bournemouth in February, I asked him why it was that, after 10 years of promoting his MMR-autism theory, he had failed to win the support of a single autism specialist, paediatrician or paediatric gastroenterologist in the UK (who is not exclusively in private practice or a beneficiary of the litigation)? He refused to answer. The Washington hearings have raised further questions. Nicholas Chadwick, now a biochemist in Manchester, told the court how he, as a postgraduate student in Wakefield’s team at the Royal Free, conducted PCR studies for measles virus on biopsy specimens of the 12 children included in the Lancet study. His studies showed that all specimens were negative (and that earlier results had shown ‘false positives’ resulting from contamination). Wakefield suppressed these results and Chadwick insisted on his name being removed from the published paper, which declared that ‘virological studies were underway’ to investigate what Chadwick had already investigated and found negative results. This information, first disclosed in Brian Deer’s 2004 television documentary, has now been presented in a court of law and still demands a full explanation (5).

As Wakefield staggers towards his date with the GMC, his supporters claim that he has been the victim of a conspiracy by the medical establishment and big pharma. The revelations in Washington seem to suggest that something approximating to the opposite is true: Wakefield appears to have been the beneficiary of a conspiracy of silence that has prevented the truth about his research from being revealed. As a junior member of the Royal Free team, Chadwick was apparently deterred from blowing the whistle by familiar concerns about his own position. Others in a position to reveal the falsity of his claims – and those emerging from the O’Leary lab – were deterred from doing so for a range of motives, from personal and professional loyalty to the inclination to give a colleague the benefit of the doubt. Still others were restricted by considerations of confidentiality and legality.

What now for Stephen Bustin? He says that, after three years of enforced silence on this subject, he is keen to get wider publicity for the message that science shows no link between MMR and autism. He has written to the Lancet summarising his findings. After years of anxiety and confusion, parents of children with autism will welcome the triumph of quality science over junk science even if we have had to wait a long time for it.

Dr Michael Fitzpatrick is a GP in London and the author of MMR and Autism: What Parents Need to Know (buy this book from Amazon UK and The Tyranny of Health: Doctors and the Regulation of Lifestyle (buy this book (buy this book from Amazon UK).

(1) ‘Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UK’, MA Afzal, J Med Virol, March 2006, 78:623-630